Through the displacement of electrons (ionization), ionizing radiation effectively disrupts molecular bonds. In living organisms, such disruption can cause extensive damage to cells and their genetic material. A characteristic type of DNA damage produced by ionizing radiation, even by a single radiation track through a cell, involves closely spaced, multiple lesions that compromise cellular DNA repair mechanisms. Although most of the cells sustaining such radiation-induced damage may be eliminated by damage response pathways, some cells are capable of escaping these pathways, propagating, and eventually undergoing malignant transformation, a crucial step in cancer development.

Ionizing radiation is an established risk factor for cancer. Studies involving the irradiation of cells and experimental animals and epidemiological studies of populations that have experienced unusually high levels of radiation exposure for medical or occupational reasons have demonstrated clear links between ionizing radiation and cancer. Examples of the latter include the 1986 Chernobyl disaster and the 1945 atomic bombings of Hiroshima and Nagasaki, Japan. In the years following those catastrophic events, thousands of people suffered radiation-induced illness and cancer.

Cancer risk is increased roughly in proportion to the amount of energy deposited in tissue (radiation dose, usually quantified in units of gray [Gy] or milligray [mGy], where 1 Gy corresponds to 1 joule of energy per kilogram of tissue). However, organs and tissues differ in their sensitivity to radiation carcinogenesis (cancer-causing ability). Cancer risk further varies by type of ionizing radiation, by gender, by age at exposure, by age and time following exposure, and by lifestyle factors, such as reproductive history and exposure to other carcinogens (e.g., tobacco smoke). On average, the bulk of radiation dose to individuals comes from natural background sources that have changed little over the span of human existence.

Sources and types of ionizing radiation

Ionizing radiation is produced by the radioactive decay of unstable isotopes of elements in rocks, soil, and body tissues and by nuclear reactions occurring in the Sun and distant stars. A major part of all exposure to such background radiation exposure is attributable to the inhalation of radon gas, which is produced by the radioactive decay of radium in rocks and soil and that, as it seeps out into the atmosphere, can become trapped and concentrated in poorly ventilated environments such as dwellings and underground mines. Radiation from radon and its radioactive decay products consists of mainly alpha particles, which have very limited ability to penetrate tissue but can damage cellular DNA in the lung if the radioactive source is inhaled and deposited in the airways. Gamma rays and X-rays, in contrast, are highly penetrating and can affect cells even when the radiation source is outside the body. Although electrons are only somewhat more penetrating than alpha particles, the immediate cause of most radiation-related damage to DNA is thought to stem from interactions with secondary electrons energized by transfer from electromagnetic or particle radiation originating outside the cell.

Different types of radiation differ somewhat in biological effectiveness per unit of dose. For example, alpha particle radiation absorbed in tissue is considered to be about 20 times more effective as a carcinogen than the same dose of gamma rays. The concept of equivalent dose, expressed in units of Sievert (Sv), was introduced for purposes of radiation protection. For gamma radiation, 1 mGy dose corresponds to 1 mSv dose equivalent, whereas for alpha radiation, 1 mGy dose corresponds to 20 mSv dose equivalent. Worldwide, the average annual human exposure to natural background radiation is 2.4 mSv per year.

Following the discovery of X-rays in 1895 by German physicist Wilhelm Conrad Röntgen and of radioactivity the following year by French physicist Henri Becquerel, medical, industrial, and military uses of radiation technology were developed that eventually led to a marked increase in human population exposure to ionizing radiation. By the early 21st century in the United States, such human-made radiation contributed about 18 percent of the total annual radiation exposure to the human population. However, radiation doses to individuals can vary widely.

As reference points, unusually high doses of ionizing radiation include dose equivalents in excess of 100 mSv. Whole-body exposures in excess of 4 Sv (4,000 mSv) are usually fatal in the absence of medical intervention, whereas much higher doses, limited to single organs or restricted parts of the body, are often used safely for treatment of cancer.

Radiation effects

The use of X-rays and radioactive materials in science, medicine, and industry led to the recognition, documented by reports of radiation burns, that radiation exposure, although helpful for the diagnosis and treatment of disease, might also be harmful, and protective measures were taken to limit exposure. It took somewhat longer for the carcinogenic potential of ionizing radiation to be recognized. Today, however, the relationship between radiation dose and cancer risk is well characterized and well quantified, and there is clear understanding of the relationship between radiation exposure, which is the energy impinging on an organism, and radiation dose, which is the amount per unit mass absorbed by a selected bit of tissue. Thus, compared to a chemical dose to a given tissue, which requires understanding of the pathways by which a given intake of the chemical carcinogen results in absorption of the chemical by the tissue of interest, radiation dose is readily estimated.

An early study comparing cancer mortality among British radiologists who had registered with a radiological society before 1920 with that among radiologists who began their practice thereafter, when the first protection recommendations were released, provided key evidence that exposure was related to risk. Although cancer death rates among radiologists registered after 1920 was comparable to death rates for practitioners across all fields of medicine, radiologists still exhibited an excess cancer risk, presumably owing to long-term radiation exposure. Experimental studies of radiation effects such as cell inactivation, mutation, and cancer have taken advantage of the experimenters’ ability to regulate, with precision, radiation doses to target cells or tissues. Similarly, epidemiological investigations of exposed populations have benefited from the ability of scientists to reconstruct individual, and even organ-specific, radiation doses. Benefits include the estimation of dose-response relationships and of the modification of such relationships by individual properties such as sex, age, lifestyle, and genetic inheritance.

Leukemia was the first human cancer for which risk was unequivocally demonstrated to increase with dose of ionizing radiation. This increase was shown among atomic bomb survivors and among a series of British patients treated by X-ray for ankylosing spondylitis, a painful form of arthritis of the spine. The thyroid gland was the first solid cancer site for which radiation dose was strongly implicated as a risk factor, based on the screening of atomic bomb survivors and of patients treated by radiation for diseases of the head and neck. Since then, radiation dose responses to gamma-ray and X-ray radiation in the under-4-Sv range have been established for all solid cancers as a group and for cancers of the breast, thyroid, stomach, colon, liver, lung, bladder, and ovary in particular. The evidence for a radiation-related risk is also persuasive for cancers of the oral cavity as a group and specifically for the salivary glands. Risk associations also have been described for esophageal cancer, nonmelanoma skin cancer (particularly basal cell skin cancer), and malignant and benign tumours of the brain and central nervous system (including glioma, meningioma, and schwannoma). Internal exposure to radon and its decay products is associated with an increased risk of lung cancer, while bone sarcoma risk is associated with radiation dose from ingested or injected radium.

There is a general tendency, with some exceptions, for dose-specific risk of radiation-related cancer to be inversely associated with exposure age. Both radiation-related and baseline cancer risk tend to increase with age following exposure, but the age-related increase for radiation-related risk may not be as steep as that for baseline cancer risk. A first full-term pregnancy at a relatively young age (e.g., before age 25 years) is protective against radiation-related breast cancer risk, even if the radiation exposure preceded the first full-term pregnancy. The interaction between smoking and radiation exposure as lung cancer risk factors is less clear. For example, some evidence indicates that radon-related excess risk (as distinguished from smoking-related risk) among uranium miners is higher for smokers than for nonsmokers. Other evidence indicates that radiation-related excess risk among atomic bomb survivors exposed to gamma radiation did not differ by smoking level.